Studies on Search for a Promising Immunopotentiative Substance for Treatment of Leprosy On several Synthesized Amphoteric Dextrans Exhibiting both of Immunopotentiative and Antiexudative Actions

• Published in: Japanese journal of leprosy Vol. 52; no. 4; pp. 200 - 216
• Main Authors: GIDOH, MASAICHI, TSUTSUMI, SADAE, KAMOHARA, SHIGEYOSHI
• Format: Journal Article
• Language: Japanese
• Published: Japanese Leprosy Association 30.12.1983
• ISSN: 0386-3980; 2185-1360
• DOI: 10.5025/hansen1977.52.200

1. The substitution of taurine-diethylaminoethylamine (DEAEAM) or DEAEAM alone for Br of BHP-activated dextran produced an amphoteric and a basic dextrans named BHP-T and D, respectively. 2. The reaction of dextran (DX) having molecular weight of 70000 (DX T-70) or 250000 with diethylaminoethylchloride (DEAECI) and followed with SO3-pyridine in formamide produced 2 amphoteric DXs (ADXs). They were named as ADXs-1 and 2, respectively. Similarly, 4 ADXs which contents of SO3H radicals were much higher than those of ADX-1 and 2 were synthesized from DX T-40. They were named as ADXs-3-6, respectively. 3. The promotive effects of these ADXs on the recoveries of T cell in thymectomized and immunodepressed guinea pigs (immunodepressed GP) were examines. The promotion was found in BHP-T (at 30mg/kg, intramuscularly), ADX-2 (at 15 or 30mg/kg, intramuscularly, at 30mg/kg, orally) or in ADX-3 (at 30mg/kg, intramuscularly). Throughout a series of these examinations, a β-1-3 glucan named ATSO which was purified from basidiomycetes exhibited the promotive action. 4. The oral dose of BHP-T (100mg/kg), BHP-D (100mg/kg), ADX-2 (30mg/kg) or ADX-3 (30mg/kg) increased the plaque forming cells (PFC) when examined by a Cunningham plaque forming test. However, the excessive high dosages of ADX-2 (30mg/kg, intramuscularly and 100mg/kg, orally) contrarily resulted in the decreases of PFC, which were presumed to be due to the hemolytic and/or fibrolytic actions of ADX-2. The intraperitoneal dose of 100mg/kg of BHP. T did not increase the counts of PFC in contrast with a marked increase when orally dosed the same dosage. 5. The intramuscular dose of ADX directing toward the foot paw to be inflamed by carrageenin more or less inhibited carrageenin-induced rat acute edema (CRAE). The inhibitory effects were stronger in ADXs-3-6 than in ADX-2. A high dosage of BHP-T (100mg/kg) exhibited the inhibitory action strongly even administered orally. Whereas, the oral dose of its DX moiety (DX T-70) enhanced the formation of edema. BHP-D as a basic DX did not inhibit CRAE. However, ATSO as a non-ADX apparently inhibited CRAE. 6. None of ADX-2, BHP-T and ATSO inhibited adjuvant-induced arthritis (AIA) which was induced by 1.5mg (dry weight) of Mycob. butyricum. Contrarily, ATSO significantly stimulated some phases of AIA. The potential to induce AIA was significantly higher in Mycob. tuberculosis, strain Aoyama B than in Mycob. butyricum. The inhibitory effect of an immunomodulative drug, CCA could not be detected in this AIA induced strongly by the high dosages of Mycob. butyricum. 7. The toxicity of ADX-3 was found to be further stronger than that of ADX-2. 8. Based on these results, the role of immunopotentiation therapy by polysaccharides in the treatment of leprosy was discussed.